Connect
MJA
MJA

Should patients with heart failure listen to their gut?

John J Atherton and Chamindie Punyadeera
Med J Aust 2020; 213 (8): . || doi: 10.5694/mja2.50797
Published online: 19 October 2020

Dysregulation of the gut microbiota may be a target for novel therapeutic approaches

Large randomised, controlled studies have found that modulating dysregulated neurohormonal systems in patients with heart failure can reduce morbidity and mortality in those with a reduced left ventricular ejection fraction (LVEF).1 However, long term clinical outcomes remain poor, and most patients are unable to achieve the target doses of guideline‐directed therapy. Further, these drugs do not resolve all the pathophysiological perturbations associated with heart failure. Interest in biomarker discovery is therefore growing, not only to facilitate earlier diagnosis and risk stratification, but also to identify novel targets for therapeutic interventions.


  • 1 Royal Brisbane and Women's Hospital, Brisbane, QLD
  • 2 University of Queensland, Brisbane, QLD
  • 3 Queensland University of Technology, Brisbane, QLD



Competing interests:

No relevant disclosures.

  • 1. Atherton JJ, Sindone A, De Pasquale CG, et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of heart failure 2018. Med J Aust 2018; 209: 363–369. https://www.mja.com.au/journal/2018/209/8/national-heart-foundation-australia-and-cardiac-society-australia-and-new-0
  • 2. Tang WHW, Li DY, Hazen SL. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol 2019; 16: 137–154.
  • 3. Niebauer J, Volk HD, Kemp M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999; 353: 1838–1842.
  • 4. Rauchhaus M, Doehner W, Francis DP, et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 2000; 102: 3060–3067.
  • 5. Hartman MHT, Groot HE, Leach IM, et al. Translational overview of cytokine inhibition in acute myocardial infarction and chronic heart failure. Trends Cardiovasc Med 2018; 28: 369–379.
  • 6. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472: 57–63.
  • 7. Tang WH, Wang Z, Fan Y, et al. Prognostic value of elevated levels of intestinal microbe‐generated metabolite trimethylamine‐N‐oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol 2014; 64: 1908–1914.
  • 8. Suzuki T, Yazaki Y, Voors AA, et al. Association with outcomes and response to treatment of trimethylamine N‐oxide in heart failure: results from BIOSTAT‐CHF. Eur J Heart Fail 2019; 21: 877–886.
  • 9. Li W, Huang A, Zhu H, et al. Gut microbiota‐derived trimethylamine N‐oxide is associated with poor prognosis in patients with heart failure. Med J Aust 2020; 213: 374–379.
  • 10. Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368: 1575–1584.
  • 11. Zhu W, Gregory JC, Org E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 2016; 165: 111–124.
  • 12. Organ CL, Otsuka H, Bhushan S, et al. Choline diet and its gut microbe‐derived metabolite, trimethylamine N‐oxide, exacerbate pressure overload‐induced heart failure. Circ Heart Fail 2016; 9: e002314.
  • 13. Chen K, Zheng X, Feng M, et al. Gut microbiota‐dependent metabolite trimethylamine N‐oxide contributes to cardiac dysfunction in western diet‐induced obese mice. Front Physiol 2017; 8: 139.
  • 14. Li X, Sun Y, Zhang X, Wang J. Reductions in gut microbiota‐derived metabolite trimethylamine N‐oxide in the circulation may ameliorate myocardial infarction‐induced heart failure in rats, possibly by inhibiting interleukin‐8 secretion. Mol Med Rep 2019; 20: 779–786.
  • 15. Costanza AC, Moscavitch SD, Faria Neto HC, Mesquita ET. Probiotic therapy with Saccharomyces boulardii for heart failure patients: a randomized, double‐blind, placebo‐controlled pilot trial. Int J Cardiol 2015; 179: 348–350.
  • 16. Mayerhofer CCK, Awoyemi AO, Moscavitch SD, et al. Design of the GutHeart‐targeting gut microbiota to treat heart failure‐trial: a phase II, randomized clinical trial. ESC Heart Fail 2018; 5: 977–984.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.